Evaluation of the Developmental Toxicity of Acetyl Cedrene

International Journal of Toxicology - Tập 25 Số 5 - Trang 423-428 - 2006
A. Lapczynski1, Daniel A. Isola2, Mildred S. Christian3, Robert M. Diener3, A.M. Api2
1Research Institute for Fragrance Materials, Inc., Woodcliff Lake, New Jersey 07677, USA.
2Research Institute for Fragrance Materials, Inc., Woodcliff Lake, New Jersey, USA
3Argus International, Inc., Horsham, Pennsylvania, USA

Tóm tắt

The developmental toxicity of acetyl cedrene (AC), a widely used fragrance ingredient, was evaluated in pregnant Sprague-Dawley rats (25/group). Gavaged dosages of 0 (corn oil), 25, 50, or 100 mg/kg/day were administered on days 7 through 17 of gestation (GDs 7 to 17). First and last day dosing suspensions were analyzed for AC content. All rats were observed daily for viability, clinical signs, abortions, and premature deliveries. Body weights were recorded at frequent intervals. Cesarean-sectioning and necropsy examinations were performed on GD 21. Uteri were examined for number and distribution of implantations, live and dead fetuses, and early and late resorptions. The number of corpora lutea in each ovary was also recorded. Fetuses were weighed and examined for gender and gross external changes and soft tissue or skeletal alterations. Totals of 25, 23, 21, and 24 rats became pregnant in the 0 (control), 25, 50 and 100 mg/kg/day groups, respectively, and analysis of dosage preparations verified that administered dosages reflected calculated dosages ±10%. No deaths or premature deliveries occurred in the study. Clinical signs included excessive salivation, which was attributed to the administration of AC. When compared to controls, significant reductions in feed consumption and body weight gains occurred only at 100 mg/kg/day. Both absolute (g/day) and relative (g/kg/day) feed consumption values were significantly decreased on GDs 7 to 12. Relative values were decreased significantly on GDs 15 to 18. Body weight gains were significantly reduced on GDs 7 to 10. Mean maternal body weights remained significantly lower than controls on GDs 9 to 14, but a marked compensatory increase in feed consumption on GDs 15 to 18 prevented further deterioration in body weight gains. No cesarean-sectioning or litter parameters were affected by dosages of AC and necropsy of the dams after cesarean section did not reveal any gross changes attributable to AC. No gross external, soft tissue, or skeletal fetal alterations (malformations or variations) were attributed by dosages AC. The average number of ossifications sites per fetus per litter did not differ among the groups. Based on these data, maternal and developmental no-observable-adverse-effect levels (NOAELs) of 50 and 100 mg/kg/day, respectively, were established for AC.

Từ khóa


Tài liệu tham khảo

10.1080/00401706.1964.10490181

10.1080/01621459.1955.10501294

IFRA -International Fragrance Association-1998IFRA Exposure Inquiry

Institute of Laboratory Animal Resources1996Guide for the care and use of laboratory animalsWashington, DCNational Academy Press

Khera KS, 1981, Fundam Appl Toxicol, 1, 13

MHW -Japanese Ministry of Health and Welfare-, 1997, MHW Ordinance, 26, 1997

OECD -Organization for Economic Cooperation and Development-1998The Revised OECD Principles of Good Laboratory Practices [C-97-186/Final]

10.1093/toxsci/58.1.1

SiegelS1956Nonparametric statistics for the behavioral sciences96104New YorkMcGraw-Hill

Snedecor GW, 1967, Statistical methods, 6, 258

Snedecor GW, 1967, Statistical methods, 6, 240

Sokal RR, 1969, Biometry, 370

Sokal RR, 1969, Biometry, 388

Staples RE, 1964, Stain Technol, 39, 61

US FDA -Food and Drug Administration-1987Good Laboratory Practice Regulations; Final Rule. 21 CFR part 58

US FDA -Food and Drug Administration-1994International conference on harmonization; Guideline on detection of toxicity to reproduction for medicinal productsFederal Register, September 22, 1994, volume 59, no. 183.

Wilson JG, 1965, Teratology: Principles and techniques, 262

Thông tin
Thông tin xuất bản

International Journal of Toxicology

Tập 25 Số 5

423-428

Thông tin tác giả